Active gonococcal infection as well as purified gonococcal lipopolysaccharide and gonococcal peptidoglycan damage human fallopian tube mucosa in organ culture and induce sloughing of ciliated cells. Subsequent to this first phase of the disease process, the nonciliated cells of the human fallopian tube mucosa endocytose gonococci and transport them across the mucosal epithelium in a process we call "parasite-directed endocytosis". The impetus for the action of these nonciliated, "Trojan horse" cells is undefined. Recently the P.I. has shown that gonococcal infection induces the production of cachectin/tumor necrosis factor (TNF) by human fallopian tube mucosa. This cytokine-lymphokine has been convincingly shown by others to be a mediator of the lethal and deleterious effects of endotoxin. In preliminary studies, the P.I. has shown that purified TNF in concentrations as low as 1 to 10 ug/ml reliably damages the fallopian tube mucosa. The proposed studies are designed to determine which, if any of the gonococcal products that damage human fallopian tube mucosa, endotoxin or peptidoglycan monomers (both B-cell activators) elicits production of TNF and might damage the mucosa indirectly by this means. The possible role of TNF in stimulating endocytosis by nonciliated cells will also be examined.